• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth.

The long-term integrity of an articulating joint is dependent upon the nourishment of its cartilage component and the protection of the cartilage surface from friction-induced wear. Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by the gene PRG4) cause the human autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP). A major feature of CACP is precocious joint failure. In order to delineate the mechanism by which lubricin protects joints, we studied the expression of Prg4 mRNA during mouse joint development, and we created lubricin-mutant mice. Prg4 began to be expressed in surface chondrocytes and synoviocytes after joint cavitation had occurred and remained strongly expressed by these cells postnatally. Mice lacking lubricin were viable and fertile. In the newborn period, their joints appeared normal. As the mice aged, we observed abnormal protein deposits on the cartilage surface and disappearance of underlying superficial zone chondrocytes. In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributed to joint failure. Purified or recombinant lubricin inhibited the growth of these synoviocytes in vitro. Tendon and tendon sheath involvement was present in the ankle joints, where morphologic changes and abnormal calcification of these structures were observed. We conclude that lubricin has multiple functions in articulating joints and tendons that include the protection of surfaces and the control of synovial cell growth.

Pubmed ID: 15719068

Authors

  • Rhee DK
  • Marcelino J
  • Baker M
  • Gong Y
  • Smits P
  • Lefebvre V
  • Jay GD
  • Stewart M
  • Wang H
  • Warman ML
  • Carpten JD

Journal

The Journal of clinical investigation

Publication Data

March 16, 2005

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR050180
  • Agency: NIAMS NIH HHS, Id: AR46249
  • Agency: NIGMS NIH HHS, Id: GM07250
  • Agency: NIGMS NIH HHS, Id: GM08613
  • Agency: NICHD NIH HHS, Id: HD07104
  • Agency: NICHD NIH HHS, Id: HD07518
  • Agency: NIA NIH HHS, Id: K08AG/AR01008

Mesh Terms

  • Animals
  • Cartilage
  • Cell Adhesion
  • Cell Proliferation
  • Cells, Cultured
  • Chondrocytes
  • Hindlimb
  • Humans
  • In Situ Hybridization
  • Joint Diseases
  • Joints
  • Mice
  • Mice, Knockout
  • Phenotype
  • Protein Structure, Secondary
  • Proteoglycans
  • Recombinant Proteins
  • Surface Properties
  • Syndrome
  • Synovial Fluid
  • Synovial Membrane